Functional Organization of the Olfactory Cortex

嗅觉丧失是许多神经退行性疾病和衰老疾病的最初迹象之一。知识 神经元结构和大脑中信息流的途径对于确定病因很重要 这可能会导致早期诊断和更好地治疗潜在的 条件过去的研究已经揭示了很多关于老鼠气味检测的机制 嗅上皮和嗅球，但很少有人知道感觉信息是如何在皮层编码。我们 以前的研究表明，来自不同类型的气味受体（OR）的输入是针对 不同但空间重叠的皮质神经元簇，每个皮质神经元似乎都接收到 来自多个OR的输入。考虑到每一种气味分子都是通过鼻子中的 不同的OR，该提案将开发和应用遗传和功能方法来测试来自 由同一种气味物质激活的不同的OR集中在皮层神经元上，以确定它们的反应 的特异性目的1：构建重组腺相关病毒（rAAV）， 跨神经元示踪剂。由于每个球肾小球代表单一类型的OR，我们将注射不同的rAAV 不同的肾小球表达不同的示踪剂在球二尖瓣和簇状细胞连接到注射 肾小球示踪剂将从球迁移到皮质，以揭示相应的皮质组织。 手术室这些研究将测试来自被相同气味激活的OR的输入是否会汇聚到皮层 神经元在目标2中，我们将检查被气味剂激活的神经元是否是那些接受会聚的神经元。 从其OR输入。此外，我们还将比较单独与联合刺激激活的皮层神经元 OR输入，以测试OR输入的组合是否塑造皮层神经元的反应特异性。在一起， 这些研究将显示不同的OR检测到的不同化学特征是如何整合到大脑皮层中的 产生不同的感知。本提案中开发的新追踪方法也将有助于 系统地分析刻板的灯泡地图是如何在皮层中地形表示的， 不同的气味质量由不同的皮层模式表示。拟议的研究非常适合 为R21机理。

Loss of smell is one of the first signs of many neurodegenerative diseases and aging disorders. Knowledge of neuronal structure and the pathways of information flow in the brain is important for identifying the cause of smell loss in diseased brains which may lead to early diagnosis and better treatment of the underlying conditions. Studies in the past have uncovered much about the mechanisms of odor detection in the mouse olfactory epithelium and bulb, but little is known about how sensory information is encoded in the cortex. We previously showed that inputs derived from different types of odorant receptors (ORs) are targeted to different but spatially overlapping clusters of cortical neurons and each cortical neuron appears to receive inputs from multiple ORs. Given that each odor molecule is detected in the nose by a combination of different ORs, this proposal will develop and apply genetic and functional approaches to test if inputs from the different ORs activated by the same odorant converge on cortical neurons to determine their response specificity. In Aim 1, we will develop recombinant adeno-associated virus (rAAV) to express different transneuronal tracers. As each bulb glomerulus represents a single type of OR, we will inject different rAAVs into different glomeruli to express a distinct tracer in bulb mitral and tufted cells connected to the injected glomeruli. The tracer will migrate from bulb to cortex to reveal the cortical organization of the corresponding ORs. These studies will test if inputs from the ORsactivatedby the same odorant converge on cortical neurons. In Aim 2, we will examine if the neurons activated by an odorant are those that receive convergent inputs from its ORs. In addition, we will compare the cortical neurons activated by separate versus combined OR inputs to test if combinations of ORinputs shape the response specificity of cortical neurons. Together, these studies will show how different chemical features detected by different ORs are integrated in the cortex to yield distinct perceptions. The new tracing method developed in this proposal will also be useful to systematically analyze how the stereotyped bulb map is topographically represented in the cortex and if different odor qualities are represented by distinct cortical patterns. The proposed studies are ideally suited fortheR21 mechanism.